EDITOR’S COMMENT: The last decade has witnessed a revolution in our understanding of how the brain works. This involves epigenetics at various levels. Until recently it was believed that neuro-computation depends of the classical mechanisms of axon spikes and local field potentials, together with a variety of G-protein-linked receptors and second messenger systems, including some involving transcription factors and new protein synthesis. The past decade has witnessed a great development in our understanding of how much of the brain's functions is controlled by a further battery of epigenetic factors. These include:

(1) DNA and histone methylation and acetylation that switch genes on and off

(2) a wide range of transcription factors that are exported beyond the synapse that produced them

(3) (most importantly,) the epigenetic activity of a multitude of non-coding RNAs (including the microRNAs that block mRNAs)

(4) carrier organelles for (these) epigenetic loads, such as exosomes.

Exosomes are small lipoprotein vesicles that bud-off from all cells and carry payloads of epigenetic molecules. These comprise varieties of RNA (including mRNAs and microRNAs), lengths of DNA, a wide variety of proteins (including transcription factors), organelles such as ion channels and receptors, lipids and others, These exosomes travel short or long distances (via blood) and are than taken up by target cells using specific membrane bound identification factors where they discharge their cargoes. These modulate (sometimes extensively) the structure and function of the recipient cell.

We now know that these epigenetic mechanisms play a fundamental role in the development, differentiation, microanatomy, plasticity and function in all neurons. Activities such as DNA-methylation are now known to play a fundamental role in disease (see Smythies 2013 for an example in schizophrenia). In addition exosomes have an important clinical aspect since pathological cells export exosomes carrying different loads from normal cells. These can be obtained from the blood and other body fluids. The scene is now a hive of activity with specific exosome-based tests being developed for a wide variety of diseases including prion diseases, Parkinson’s disease, Alzheimer, multiple sclerosis, schizophrenia and cancer (Tislioni et al. 2014). Furthermore exosomes can be made to carry therapeutic molecules to specific locations.

This Theme Issue presents 18 selected reviews and original research from peer-acknowledged experts in their respective disciplines on some of the highlights in this nascent and rapidly developing field.

The discoveries discussed in this Theme Issue have revolutionized our view of how the brain works in both health and disease. They have radically altered our understanding of the molecular components of many diseases involving all systems and have suggested lines of diagnosis and treatment which are just beginning to be realized.